Hydrogen Bromide → Codeine

Participants

Reaction Conditions

Reaction Steps

A solution of thebaine (6.22 g) in glacial acetic acid (20 ml) was stirred at 15° C. and treated dropwise over 5 minutes with a 45% w/v solution of hydrogen bromide in glacial acetic adid (12.6 ml, 3.5 equivalents). TLC examination of a sample withdrawn 15 minutes after completion of the addition showed that the reaction was complete. The reaction mixture was then added slowly to a stirred slurry of sodium carbonate (62.5 g) in water (150 ml) keeping the temperature below 5° C. Methanol (250 ml) and water (100 ml) were added and the crude codeinone was reduced by portionwise addition of sodium borohydride (0.76 g) with stirring at 20° C. A sample was taken after 16 hours and the reduction was found to be complete (TLC). The reaction mixture was then filtered to remove inorganic solids and the filtrate was concentrated under reduced pressure until most of the methanol had been removed. The residual solid in the filter was washed with chloroform (100 ml) and the chloroform wash was used in two equal portions to extract the above aqueous concentrate. The chloroform extract was washed with water (25 ml), dried over sodium sulphate and the solvent removed under reduced pressure to give the title compound (3.88 g) identical by TLC and GLC with an authentic sample.

Provenance & Evidence